SPECIFIC AIMS: 1) Study gene-environment interaction in regards to tissue inflammation, and history of prostatis and sexually transmitted diseases.2) Identify gene expression profiles that are uniquely associated with prostate cancer in African-American males.3) Develop a molecular signature of prostate tumors that differentiates active smokers and non-smokers.4) Correlate nicotine and IGF-1 serum concentrations with tumor tissue markers such as phosphorylated Akt or phosphorylation of genes regulated by Akt.5) Examine the association between allele variant genes and prostate cancer using the case-control design of the Maryland Prostate Cancer Study.6) Examine the relationship between allele variant genes and morphologic, molecular, clinical, prognostic and outcome endpoints among cases.7) Establish phenotype-genotype relationships for low-penetrance genes and identify molecular profiles that are associated with at-risk genotypes.The greater Baltimore area has an African-American and Caucasian population of similar size, which makes this area most suitable to study a cancer health disparity among these two race/ethnic groups. We designed a new protocol that proposes a combination of epidemiology-based and laboratory-based research to investigate causes of prostate cancer. The protocol has been approved by the NCI Protocol Review & Monitoring Committee, the NCI Special Studies Institutional Review Board, and by the University of Maryland Institutional Review Board. We started recruitment for a case-control study in February, 2005. The study will include 400(-800) prostate cancer cases and a sample of 400(-800) population-based controls. The participants will be an equal number of African-American and Caucasian males who reside in Baltimore City and surrounding areas. The cases will be recruited at two Baltimore hospitals, the Veterans Affairs Medical Center and the University of Maryland Medical Center, over a 5-year period. Cases will have pathologically confirmed incident prostate cancer. The enrollment of controls will begin concurrently with case accrual, and will continue for 5 years. Controls will be identified through the Department of Motor Vehicle database and will match cases by age, race, and residency. The study will involve the administration of two questionnaires and the collection of blood from all study subjects. Fresh-frozen tumor specimens will be obtained from 30-50% of the cancer patients. The study will be supported by the epidemiological infrastructure that has been developed by our resource contractor at the University of Maryland for an ongoing lung cancer case-control study. We will recruit the controls using a double eligibility criterion. The population-based controls for the prostate cancer study will also be eligible for the ongoing lung cancer study. This is possible because of the very similar age distribution of lung and prostate cancer patients in the two studies, and because the controls in the prostate study meet the eligibility criteria of the lung study. The primary questionnaire has been developed for the lung study and evaluates family cancer history, tobacco use, medication, occupational history, and socioeconomic status. The supplemental questionnaire, which has been reviewed and approved by the Technical Evaluation of Questionnaires Committee, DCEG/NCI, will assess additional risk factors for prostate cancer, such as anthropometry, dietary factors, sexually transmitted disease, medical history, and family medical history. Subjects will be excluded from our study if they are severely ill, are institutionalized, have a racial/ethnic background other than being of African-American or Caucasian descent, are infected with HIV, Hepatitis B or C by self-report, or are physically or mentally unable to sign a consent form and complete the survey. Subjects must be born in the United States, are age 40-90 years, and have a residency in the greater Baltimore area at the time of recruitment.